Cord blood lead level in an urban inner-city hospital.

Lead levels were measured by inductively coupled plasma mass spectrometry (ICP-MS) in umbilical cord blood samples of 150 neonates in an urban inner-city hospital. The mean (SD) gestation and birth weight of our cohort were 38.8 (1.7) weeks and 3,217 (519) grams. There were 89% African-Americans, 53% males and 79% were born via vaginal delivery. Mean (SD) maternal age was 24.5 (5.8) years. History of drug abuse and smoking was reported in 8.7% and 10.7% respectively, with only 1 mother reporting a history of high lead level in childhood. Prenatal vitamin intake was reported in 99.3%. Cord blood lead level was available in 144 patients, with lead level of <1µg/dL seen in 141 (97.9%) and>1 in 3 (2.1%) patients. No patient had cord blood lead level of >2µg/dL. High lead levels during childhood in high-risk urban population, however, suggest the need for intensive efforts for prevention of environmental exposure to lead in early childhood.

High-dose chemotherapy and adoptive immunotherapy in the treatment of recurrent pediatric brain tumors.

Pediatric patients with recurrent brain tumors have a poor prognosis and limited therapeutic options. We investigated the use of high-dose chemotherapy with adoptive immunotherapy for recurrent brain tumors. Three pediatric patients with recurrent brain tumors received high-dose chemotherapy. This was followed by adoptive transfer of ex-vivo expanded T-cells. The T-cells were generated from peripheral blood after immunization with autologous cancer cells. The objectives of this study included (1) establishing the safety and feasibility of this potential treatment, (2) measuring changes in immune response after high-dose chemotherapy and adoptive immunotherapy, and (3) determining whether adoptive immunotherapy would be able to translate into a clinical response. Immune function was tested in all patients at the time of enrollment into the study. Humoral responses to recall antigens delayed-type hypersensitivity (DTH) were intact in all patients. After immunizing patients with autologous cancer cells, peripheral blood lymphocytes were harvested and activated with anti-CD3, expanded in-vitro, and infused post-autologous transplant. Patients received at least three doses of the vaccine, each consisting of an intradermal administration near a draining lymph node at biweekly intervals. Toxicity was limited and well tolerated in all patients. All three patients showed a tumor-specific immune response by serial imaging. Responses were durable at 16, 23, and 48 months, respectively.

Early deaths in childhood cancer.

BACKGROUND: Deaths prior to or shortly after the diagnosis of childhood cancer may reflect inadequacies in detection and appropriate referral for care. This study was performed to determine the extent of and factors associated with early death in childhood cancer. PROCEDURE: Patients with of primary cancer, aged <20 years at diagnosis, were identified from the SEER data (n = 23,470) from 1973 to 1995. Early deaths were defined as cases identified by 1) death certificate, 2) autopsy report, or 3) death within 1 month of initial diagnoses (n = 481). Cause of death was determined by ICD-8 and -9 codes. Age at diagnosis, year of diagnosis, morphology, site of disease, race, and gender were evaluated for association with early death. RESULTS: Age <1 year at diagnosis (6.2% early deaths), being diagnosed earlier in the observation period, and a diagnosis of a brain tumor, neuroblastoma, leukemia, or liver tumor were associated with increased early death. Gender and race were not associated with early death. Among the cases for whom the malignant diagnosis was made at the time of death (n = 119), the cause of death was nonmalignant for 36. For 22 of these cases the malignancy was an incidental finding and appeared not to contribute directly to the cause of death. Among these patients, 11 had neuroblastoma, 9 being <1 year of age. CONCLUSIONS: A decrease in the proportion of early deaths associated with childhood cancer has occurred during the past 2 decades. This decrease may reflect earlier diagnosis or improved imaging capabilities, surgical techniques, medical therapy, and supportive care. Awareness among pediatricians, general practitioners, and emergency physicians is warranted, with a focus on high-risk groups for early detection among childhood cancer patients.

Differential effects of low-level lead exposure on the natural isozymes of erythrocyte 5'-nucleotidase.

OBJECTIVE: Erythrocyte pyrimidine 5'-nucleotidase (Pyr-5'-N) is highly sensitive to heavy metal inactivation in vitro and in vivo, and a number of studies have verified its usefulness as a biomarker of acute and chronic lead exposures. Retrospective and prospective studies attempted to determine whether the known linearity of Pyr-5'-N inhibition by lead concentrations above 40 microg/dL whole blood might continue into the lowest range of exposures now considered to be toxic in children (<10-20 microg/dL), thereby extending its value as a biomarker of lead exposure. DESIGN: Activities of Pyr-5'-N and a lead-insensitive isozyme, deoxyribonucleotidase (d-5'-N), were compared to blood lead and free erythrocyte protoporphyrin (FEP) concentrations. RESULTS: Pyr-5'-N activities in erythrocytes from 70 children displayed an inverse linear correlation with whole blood lead of 1-35 microg/dL, whereas d-5'-N did not correlate. There was no apparent minimum threshold for Pyr-5'-N inhibition by lead. CONCLUSIONS: Linearity of Pyr-5'-N inhibition by lead extends throughout the range of clinical concern in pediatric cases. Pyr-5'-N/d-5'-N activity ratios may provide an even more sensitive, internally controlled biomarker of low-level lead overburden, since both isozymes vary comparably in activity as a function of reticulocytosis and mean red cell age.

Permanent I-125 brain stem implants in children.

Between 1988 and 1997, 28 children have had iodine-125 implants for CNS tumors performed in our institution. Ten had stereotactic implantation in the brain stem region, and nine had the diagnosis of brain stem glioma (8 diffuse pontine, 1 midbrain tumor). Their ages ranged from 1.8 to 12 years. All patients had histological confirmation of malignancy (7 high-grade glioma, 2 low-grade glioma, 1 PNET). Diffuse pontine glioma patients received external beam radiation (50 Gy) followed by a fractionated stereotactic boost of 3 Gyx4 fractions. After 4-6 weeks, patients were reevaluated for stereotactic interstitial I-125 therapy. The planned implant dose was 82.9 Gy to the enhancing tumor (4 cGy per h). Preliminary results indicated that no surgical complications were associated with the catheter placement. Four patients have died (7-9 months from diagnosis) and four patients remain alive (5-38 months from diagnosis, median 10 months). Two autopsies confirmed the presence of progressive glioblastoma multiforme and intralesional necrosis. In one patient who received an implant alone for midbrain LGA, necrosis without tumor was found on biopsy after 36 months. He was successfully treated with hyperbaric oxygen therapy. The implementation of permanent I-125 implants appears to have a role in the management of pediatric CNS malignancy. This study confirms the results of previous reports regarding the safety of stereotactic interstitial brachytherapy in the brain stem. Tumor control for patients with high-grade brain stem glioma remains poor even with high focal radiation doses.

Hyperbaric oxygen therapy for radiation-induced brain injury in children.

BACKGROUND: Radiation-induced necrosis (RIN) of the brain is a complication associated with the use of aggressive focal treatments such as radioactive implants and stereotactic radiosurgery. In an attempt to treat patients with central nervous system (CNS) RIN, ten patients received hyperbaric oxygen treatment (HBOT). METHODS: Patients presented with new or increasing neurologic deficits associated with imaging changes after radiotherapy. Necrosis was proven by biopsy in eight cases. HBOT was comprised of 20-30 sessions at 2.0 to 2.4 atmospheres, for 90 minutes-2 hours. Sites of RIN included the brain stem (n = 2), posterior fossa (n = 1), and supratentorial fossa (n 7). Histologic types included brain stem glioma (n = 2), ependymoma (n = 2), germinoma (n = 2), low grade astrocytoma (n = 1), oligodendroglioma (n = 1), glioblastoma multiforme (n = 1), and arteriovenous malformation (n = 1). RESULTS: Initial improvement or stabilization of symptoms and/or imaging findings were documented in all ten patients studied and no severe HBOT toxicity was observed. Four patients died, with the cause of death attributed to tumor progression. Five of six surviving patients were improved by clinical and imaging criteria; one patient was alive with tumor present at last follow-up. CONCLUSIONS: HBOT may prove to be an important adjunct to surgery and steroid therapy for CNS RIN.

A new filter paper method to measure capillary blood lead level in children.

OBJECTIVE: To develop and evaluate a new filter paper method to determine capillary blood lead levels accurately in children. DESIGN: Paired comparison of lead levels determined in capillary whole blood dried on filter paper with lead levels in venous whole blood samples determined by a reference method. SETTING: Children's Hospital of Michigan clinics, Detroit. PATIENTS: One hundred children aged 9 months to 6 years. INTERVENTIONS: Lead concentrations determined in capillary whole blood samples dried on filter paper were compared with concentrations measured in paired venous whole blood samples by a reference method. MAIN OUTCOME MEASURES: Comparability of the two lead assay methods was assessed with the concordance coefficient. The sensitivity, specificity, and positive predictivity of the capillary filter paper method relative to the reference method were determined at three intervention decision concentrations of blood lead defined by the Centers for Disease Control and Prevention. RESULTS: There was high agreement between the two assay methods, with a concordance coefficient of O.96. The capillary filter paper assay had a sensitivity of 90% and specificity of 90% for differentiating blood lead levels of 0.48 mumol/L (10 micrograms/dL) or more. Blood lead levels of 0.72 mumol/L (15 micrograms/dL) or more and 0.96 mumol/L (20 micrograms/dL) or more were identified with 98% and 94% sensitivity and 98% and 99% specificity, respectively. Positive predictivity was 93%, 98%, and 97%, respectively, at the three blood lead concentration decision points. CONCLUSION: The capillary filter paper method for blood lead analysis described herein provides a convenient, sensitive, accurate, and inexpensive method to examine children for elevated blood lead levels.

Lead poisoning and thalassemia trait or iron deficiency. The value of the red blood cell distribution width.

The cause of microcytosis and anemia in lead poisoning was investigated using red blood cell distribution width as a screening parameter in 21 consecutive patients with lead poisoning and seven nonrandomly selected patients with iron deficiency and lead poisoning. Of the 21 consecutive patients, 11 had microcytosis as defined by a mean corpuscular volume of less than 72 fL, nine had thalassemia trait (alpha or beta), one had both alpha thalassemia trait and iron deficiency, and one had iron deficiency. The red blood cell distribution width was less than 17.0 in those with thalassemia trait and greater than 17.0 in the iron-deficient subjects. Results of our study suggest that microcytosis in children with lead poisoning is due to coexistent iron deficiency or thalassemia trait. The red blood cell distribution width may be of value in the rapid assessment of the cause of microcytosis in children with lead poisoning.

Seasonal clustering of transient erythroblastopenia of childhood.

In a prospective study over two years, a clustering of transient erythroblastopenia of childhood (TEC) and aplastic crises in patients with hereditary hemolytic anemia was noted during the fall and winter months. Despite this clustering, evidence for human parvovirus infection was found only in aplastic crises in patients with hemolytic anemia but not in children with TEC. The seasonal clustering noted in the small group of patients in the prospective study was corroborated by a retrospective review of 39 consecutive patients with TEC seen in our institution over a five-year period.

Acute otitis media in children: are decongestants or antihistamines necessary?

This study was designed to investigate the efficacy of a decongestant-antihistamine preparation in combination with antibiotic treatment of acute otitis media. The effectiveness of a new Dimetapp (DIM) preparation was assessed in comparison with each of its components (brompheniramine maleate [BPM] and phenylephrine hydrochloride [PEH] as well as a placebo (PL) vehicle in the treatment of acute otitis media. In a randomized double blind study, 98 children were treated in the emergency department or outpatient medical clinics at Children's Hospital of Michigan with amoxicillin and either DIM, BPM, PEH, or PL. They were evaluated at two weeks by clinical examination, pneumatoscopy, and tympanometry. Fifty-eight patients (59%) continued to have evidence of fluid in the middle ear. These patients were continued on the test medications for another two weeks and then reevaluated. There were significant differences between the treatment groups (DIM, BPM, and PEH) and the control PL group; the patients receiving Dimetapp or placebo fared better than those receiving BPM or PEH. However, there was no difference in the overall response between Dimetapp and placebo. Antihistamine-decongestant therapy does not appear to be necessary in the treatment of acute otitis media in children.